Human G6PD: Recent Origin of Alleles That Confer Malarial Resistance

Rcjohnsen rcjohnsen at
Sun Jul 22 01:32:18 EST 2001

Scince 20 July 2001 
Vol. 293 No. 5529  
Haplotype Diversity and Linkage Disequilibrium at Human G6PD: Recent Origin of
Alleles That Confer Malarial Resistance 

Sarah A. Tishkoff,12* Robert Varkonyi,2 Nelie Cahinhinan,2 Salem Abbes,3 George
Argyropoulos,4 Giovanni Destro-Bisol,5 Anthi Drousiotou,6 Bruce Dangerfield,7
Gerard Lefranc,8 Jacques Loiselet,9 Anna Piro,10 Mark Stoneking,11 Antonio
Tagarelli,10 Giuseppe Tagarelli,10 Elias H. Touma,9 Scott M. Williams,12 Andrew
G. Clark2
The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in
humans are highly correlated with the prevalence of malaria. These "deficiency"
alleles are thought to provide reduced risk from infection by the Plasmodium
parasite and are maintained at high frequency despite the hemopathologies that
they cause. Haplotype analysis of "A" and "Med" mutations at this locus
indicates that they have evolved independently and have increased in frequency
at a rate that is too rapid to be explained by random genetic drift.
Statistical modeling indicates that the A allele arose within the past 3840 to
11,760 years and the Med allele arose within the past 1600 to 6640 years. These
results support the hypothesis that malaria has had a major impact on humans
only since the introduction of agriculture within the past 10,000 years and
provide a striking example of the signature of selection on the human genome.  
1 Department of Biology, Biology/Psychology Building, University of Maryland,
College Park, MD 20742, USA. 
2 Institute of Evolutionary Genetics, Department of Biology, Pennsylvania State
University, University Park, PA 16802, USA. 
3 Faculty of Medicine and Pasteur Institute, Tunis, Tunisia. 
4 Pennington Biomedical Research Center, Louisiana State University, Baton
Rouge, LA 70808, USA. 
5 Department of Human and Animal Biology, University "La Sapienza," Rome,
6 Department of Biochemical Genetics, The Cyprus Institute of Neurology and
Genetics, Nicosia, Cyprus. 
7 Department of Human Genetics, South African Institute of Medical Research,
University of the Witwatersrand, Johannesburg, South Africa. 
8 University of Sciences and CNRS, Montpellier, France. 
9 University St. Joseph, Beirut, Lebanon. 
10 Istituto di Medicina Sperimentale e Biotecnologie-CNR, Mangone (Cosenza),
11 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. 
12 Department of Microbiology, Meharry Medical College, Nashville, TN 37208, US

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